Friedel-Crafts acylations are a well-known class of reactions with a great industrial importance for the preparation of aryl ketones by acylation of arenes (cf. e.g. the textbook M. B. Smith and J. March, “March's Advanced Organic Chemistry” 2001, 5th edition, Ed. John Wiley & Sons, pp. 712-716, and reviews cited therein). Reagents used are not only acyl halides but also carboxylic acids, esters, anhydrides, and ketenes (cf. e.g. R. C. Larock, “Comprehensive Organic Transformations” 1989, VCH: NY, p. 315; and B. C. Ranu et al., J. Org. Chem. 1996, vol. 61, p. 9546). A general reaction scheme could be:
where ArH represents a Friedel-Crafts aromatic substrate and RCOZ represents a Friedel-Crafts acylating agent selected from those mentioned above.
Friedel-Crafts acylations are generally performed using a Lewis acid catalyst, commonly AlCl3. However, there are several drawbacks associated with this type of reactions. Friedel-Crafts acylations are not truly catalytic reactions, as they actually consume one molar equivalent of AlCl3 per mole of reactant. The net result is massive usage of AlCl3 and problems associated with disposal of salts and oxide by-products. In fact, the isolation of the product typically is carried out by quenching the reaction mixture with water. The hydrolysis process generates a large amount of aqueous solutions and suspensions containing aluminum salts, which requires additional treatment steps for eventual disposal of those solutions and suspensions, and which significantly increases the cost of the process.
Another drawback derived from the industrial application of Friedel-Crafts reactions relates to the solvents used. Common solvents for the reaction include chlorine-containing solvents such as methylene chloride or 1,2-dichloroethylene, and volatile hydrocarbon solvents.
In today's society the introduction of cleaner technologies in industry (the so-called “Green Chemistry”) has become a major concern. Thus, the search for alternatives to environmentally damaging solvents has become a topic of highest priority. In the past few years, ionic liquids have received an upsurge of interest as green solvents, mainly as replacements for conventional media in chemical processes.
Ionic liquids are organic salts with melting points under 300° C., often under room temperature. The most common cations in ionic liquids are imidazolium and pyridinium derivatives, although phosphonium and tetraalkylammonium derivatives often can also be used. Some suitable anions for ionic liquids are Cl−, Br−, I−, PF6−, CF3CO2−, CH3CO2−, CF3CO2−, SO42−, NO3−, and AlCl4−.
Ionic liquids have several properties that make them suitable as potential solvents for synthesis. They are liquids in a wide temperature range. They do not have measurable vapor pressure, therefore reactions can be carried out in closed reactors without any vapor release to the atmosphere. They show very good dissolution properties for most organic and inorganic compounds. They act as Brönsted acids, Lewis acids and/or superacids. Usually they have a high thermal stability up to 200° C. They are non-flammable, not expensive and easy to prepare.
The use of some ionic liquids in Friedel-Crafts acylations carried out with conventional Friedel-Crafts catalyst is known in the art and some patent applications on the subject have been published. Patent application WO 99/19288 describes a somewhat special Friedel-Crafts acylation, carried out in the presence of a complex catalytic ionic liquid system consisting of a Lewis acid (e.g. FeCl3) and a compound of formula QCl, Q being an organic cation.
Several alternative materials to Lewis acids have been proposed as catalysts for conventional Friedel-Crafts acylations, including zeolites, superacids, the lithium perchlorate/lanthanum triflate system, etc. But these catalysts are generally effective only under restrictive circumstances (cf. e.g. A. Kawada et al., Chem. Commun. 1996, p. 183; A. Kawada et al., Synlett, 1994, p. 545; and R. Sreekumar et al., Synth. Commun. 1997, vol. 27, p. 777). Zeolites have also been proposed as catalyst for Friedel-Crafts acylations in ionic liquids (cf. WO 03/028882). Thus, from what is known in the art it is derived that the provision of a reaction system for Friedel-Crafts acylations which use neither toxic solvents nor conventional Friedel-Crafts catalysts would be of great interest in industry.